Synthesis of chiral salan ligands with bulky substituents and their application in Cu-catalyzed asymmetric Henry reaction

Abstract

Several new chiral N,N’-dimethylated salan ligands with bulky substituents were synthesized and their in-situ generated Cu(II) complexes were evaluated in the asymmetric Henry reaction. Substituents on the aryloxide moieties of these ligands were found to show remarkable effect on the enantioselectivity. Cu(II) complex generated from the ligand with 1,1-diphenylethyl groups at the ortho-position of the aryloxide moieties and Cu(OAc)2·H2O was found to show good catalytic performance, giving the 2-nitro-1-phenylethanol product in 85% yield with 94% ee in the presence of TEA in THF at -20 °C. The catalyst systems were examined with different aldehydes and the corresponding products were obtained in good yields (up to 94%) with 85% to 95% ee in the presence or absence of TEA. Diastereoselective reactions using nitroethane as the nucleophile afford syn-β-nitroalcohols in good yields (48%-66%) with good dr (up to 11.5:1 syn/anti) and high ee values (92%-96%).